Stress was found to decrease endorphins as well as bombesin in the periaqueductal gray matter (PAG) and a number of other brain regions regulating pain input. Substance P levels were not altered, however, by this manipulation. Microinjections of beta-endorphin, morphine, neurotensin, VIP and bombesin in the PAG produced profound analgesia in the rat. Somatostatin, cholecystokinin, TRH, bradykinin, and substance P had no analgesic activity. Systemic injections of opiates were found to enhance dopaminergic activity using behavioral and biochemical procedures. Dopaminergic zona compacta neurons increased their basal firing rates following morphine while zona reticulata neurons decreased their firing rates. Opiate receptors have unique laminar distributions in the rat cerebral cortex.